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Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype
INTRODUCTION: About 66% of chromosomal microdeletions and microduplications associated with pathological conditions are inherited [Smajlagić D. et al., 2021]. The mechanisms of incomplete penetrance and variable expressivity of CNV are not fully understood. The presence of concomitant CNVs in the ge...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cambridge University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9566420/ http://dx.doi.org/10.1192/j.eurpsy.2022.968 |
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author | Belyaeva, E. Kashevarova, A. Drozdov, G. Fedotov, D. Lebedev, I. |
author_facet | Belyaeva, E. Kashevarova, A. Drozdov, G. Fedotov, D. Lebedev, I. |
author_sort | Belyaeva, E. |
collection | PubMed |
description | INTRODUCTION: About 66% of chromosomal microdeletions and microduplications associated with pathological conditions are inherited [Smajlagić D. et al., 2021]. The mechanisms of incomplete penetrance and variable expressivity of CNV are not fully understood. The presence of concomitant CNVs in the genome of healthy parents may have a modifying effect. OBJECTIVES: Identification of additional CNVs in healthy carriers with 7q31.1 microdeletions. METHODS: CNVs were revealed by Agilent Technologies 60K microarray and confirmed by qPCR. RESULTS: We examined 3 families with inherited 7q31.1 microdeletions affecting only the IMMP2L gene, which is associated with intellectual disability, developmental delay and autism spectrum disorders. Family 1: Proband has intellectual disability, developmental delay, sensorimotor alalia. Microdeletion was inherited from the father, and a healthy sibling is also a carrier of rearrangement. In sibs, additional CNVs were identified: arr[hg19]: 4q31.21(144722583_144939143)×3; 9p12p11.2(43588066_43836428)×3; 16p11.2(32066967_33773163)×1; and 17q21.31(44199517_44577208)×3. Family 2: Proband suffers from development delay, speech disorder and autism. Microdeletion was of paternal origin. The father additionally demonstrated microduplication 16p11.2p11.1(33967926-35204414)×3. Family 3: Proband was diagnosed with development delay and cerebral palsy. The mother is a carrier of a similar 7q31.1 microdeletion; two concomitant CNVs were identified in her karyotype: 9p13.1(39176840_40614884)×3; and 16p11.2p11.1(32833891_35204414)×3. Thus, healthy parents in 3 families have CNV in a common region 16p11.2, which contains the TP53TG3 gene. It is important that TP53TG3 expression is associated with epistatic CNV-CNV interactions [Sun, Kardia 2010]. CONCLUSIONS: Multiple CNVs in apparently healthy carriers of IMMP2L microdeltions may suppress disease phenotype due to the epistatic CNV-CNV interaction. This study was supported by Russian Science Foundation, grant no. 21-75-00112. DISCLOSURE: No significant relationships. |
format | Online Article Text |
id | pubmed-9566420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95664202022-10-17 Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype Belyaeva, E. Kashevarova, A. Drozdov, G. Fedotov, D. Lebedev, I. Eur Psychiatry Abstract INTRODUCTION: About 66% of chromosomal microdeletions and microduplications associated with pathological conditions are inherited [Smajlagić D. et al., 2021]. The mechanisms of incomplete penetrance and variable expressivity of CNV are not fully understood. The presence of concomitant CNVs in the genome of healthy parents may have a modifying effect. OBJECTIVES: Identification of additional CNVs in healthy carriers with 7q31.1 microdeletions. METHODS: CNVs were revealed by Agilent Technologies 60K microarray and confirmed by qPCR. RESULTS: We examined 3 families with inherited 7q31.1 microdeletions affecting only the IMMP2L gene, which is associated with intellectual disability, developmental delay and autism spectrum disorders. Family 1: Proband has intellectual disability, developmental delay, sensorimotor alalia. Microdeletion was inherited from the father, and a healthy sibling is also a carrier of rearrangement. In sibs, additional CNVs were identified: arr[hg19]: 4q31.21(144722583_144939143)×3; 9p12p11.2(43588066_43836428)×3; 16p11.2(32066967_33773163)×1; and 17q21.31(44199517_44577208)×3. Family 2: Proband suffers from development delay, speech disorder and autism. Microdeletion was of paternal origin. The father additionally demonstrated microduplication 16p11.2p11.1(33967926-35204414)×3. Family 3: Proband was diagnosed with development delay and cerebral palsy. The mother is a carrier of a similar 7q31.1 microdeletion; two concomitant CNVs were identified in her karyotype: 9p13.1(39176840_40614884)×3; and 16p11.2p11.1(32833891_35204414)×3. Thus, healthy parents in 3 families have CNV in a common region 16p11.2, which contains the TP53TG3 gene. It is important that TP53TG3 expression is associated with epistatic CNV-CNV interactions [Sun, Kardia 2010]. CONCLUSIONS: Multiple CNVs in apparently healthy carriers of IMMP2L microdeltions may suppress disease phenotype due to the epistatic CNV-CNV interaction. This study was supported by Russian Science Foundation, grant no. 21-75-00112. DISCLOSURE: No significant relationships. Cambridge University Press 2022-09-01 /pmc/articles/PMC9566420/ http://dx.doi.org/10.1192/j.eurpsy.2022.968 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstract Belyaeva, E. Kashevarova, A. Drozdov, G. Fedotov, D. Lebedev, I. Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
title | Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
title_full | Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
title_fullStr | Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
title_full_unstemmed | Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
title_short | Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
title_sort | concomitant cnvs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype |
topic | Abstract |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9566420/ http://dx.doi.org/10.1192/j.eurpsy.2022.968 |
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